New Gene-Hunting Tricks

Last week, researchers in the United States and France announced a surprising discovery: a single genetic variation is responsible for 18 to 37 percent of Parkinson’s disease cases in Ashkenazi Jews and North African Arabs. While some unusual forms of Parkinson’s are carried in families, scientists had thought genetics played only a minor role in most cases of the disease.

The discovery of the gene variation, which researchers think originated in a single person in the Middle East approximately 2,000 years ago, is important in understanding the causes of Parkinson’s. It also reflects a growing tactic used by those hunting for the causes of diseases.

More and more scientists are studying populations of specific ancestry in order to hunt down genes linked to complex diseases, such as diabetes and asthma, as well as diseases such as Parkinson’s, which were not thought to have a strong genetic component.

In the past, geneticists have searched for genes involved in a few rare diseases, such as Huntington’s disease, in which a defect in a single gene causes the disorder. The technique works for these diseases because, in a small population with little genetic variation, it is relatively easy to identify the specific genetic difference that distinguishes people with the disease from those without it.

But finding genetic causes in more common illnesses caused by many genes interacting has been far harder. Now an explosion in genetic information – led by better genotyping technologies that allow scientists to analyze thousands of different genetic markers in each individual – is making it possible to study more complex diseases.

Population geneticists are particularly enthusiastic about studying the genetic signatures of two types of communities: so-called “founder” populations, such as Ashkenazi Jews and French Canadians, in which only a few ancestors contributed to the population; and admixture populations, in which two historically separate populations have mingled, such as African Americans, who have both African and European roots.

“If you’re looking at a recently mixed population or a population with recent founder affects, the genome is a lot simpler,” says David Reich, a geneticist at Harvard Medical School in Boston. “In these populations, the genome comes in big chunks of shared ancestry.”

That makes genetic studies more efficient, because scientists have to sift through fewer chunks of DNA. Because founder populations were established by only a few people, these groups have higher levels of genetic homogeneity. That means there are fewer causes for each disease, which makes it easier to find specific causes, says Reich.

This is the case in the recent Parkinson’s study. Researchers found that a single genetic mutation is responsible for a relatively large percentage of cases in the two groups under study. Within the Ashkenazim, 18 percent of diseased people carried the mutation, compared with just 1 percent of healthy people. Thirty percent of North Africans with Parkinson’s carried the mutation, compared with 3 percent of healthy people. Scientists say the surprising impact of this gene in Parkinson’s suggests that variations in this or other genes may play a role in the disease in other populations as well.

The findings also open up the possibility of genetic testing and counseling in these groups. While gene testing for diseases that have no known cure, such as Parkinson’s, is controversial, Laurie J. Ozelius, a molecular geneticist at Albert Einstein College of Medicine of Yeshiva University in the Bronx, who was involved in the research, says testing still could have some advantages. “People who come to the doctor [with symptoms of Parkinson’s] already have a lot of degeneration. Now we can look at [earlier] stages of the disease,” she says. “If we find treatments that slow the disease, it’s better to identify a gene carrier so we can start the treatment earlier.”

Susan B. Bressman, senior investigator of the report and a neurologist at Einstein, says that having a group with a known risk for Parkinson’s will aid in future studies of the disorder. Because not everyone with the mutation will go on to develop the disease, scientists can try to identify the genetic or environmental factors that put some people at greater risk. Scientists could also test potential neuroprotective drugs in this group much more efficiently than in a general population.